efficacy and safety study of autologous hematopoietic stem cell transplantation to treat new onset type 1 diabetes

Conditions: Type 1 Diabetes

Summary: type 1 diabetes is an autoimmune disease and results from t cell autoimmunity mediated destruction of the majority of insulin-producing pancreatic β-cells. hence,the development of new therapies to control t cell autoimmunity, and to preserve the remaining β-cell function will be of great significance in managing patients with type 1 diabetes autologous nonmyeloablative hematopoietic stem cell transplantation (ahst) has been tested for the treatment of patients with new onset of type 1 diabetes. this therapeutic strategy can result in exogenous insulin independence by destroying pathogenic memory t cells and preserving the remaining β-cell function. however, little is known about the efficacy of ahst in the dynamics of immunocompetent cell reconstitution and how the reconstituted immune system regulates β-cell specific antibody response. furthermore, many chinese patients at diagnosis of type 1 diabetes have progressed to develop diabetic ketoacidosis (dka). whether treatment with ahst could still achieve adequate glycemic control and preserve the β-cell function and what the factors are associated with the therapeutic efficacy have not been explored. this is a phase ⅱ clinical trial in patients who have been diagnosed with type 1 diabetes within the previous 12 months.this study is to determine: * the effects of autologous hematopoietic stem cell transplantation on the reconstitution of immune system * β-cell preservation following stem cell transplantation * the potential factors affecting efficacy of stem cell transplantation * whether this new therapy is safe.

patients diagnosed with type 1 diabetes within the previous 12 months will be recruited into this study.hematopoietic stem cells were mobilized with cyclophosphamide (cy, 2.0g/m2) and granulocyte colony stimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. the cells were infused after conditioning with cy (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). all the included patients undergoing ahst complied with blood glucose self-monitoring and scheduled medical appointments.their blood samples were obtained for measuring the frequency of lymphocytes and the levels of plasma hemoglobin a1c (hba1c), serum c-peptide, islet antibodies, and cytokines longitudinally. ages eligible for study: no more than 35 years genders eligible for study: both islet autoantibodies eligible for study: positive for glutamic acid decarboxylase antibody (gada), protein tyrosine phosphatase antibody (ia-2a), islet cell antibody (ica) and/or insulin autoantibody (iaas)

Eligibility criteria:
inclusion criteria: * diagnosis of diabetes according to the guidelines of the world health organization 1999 * the duration of diabetes is no more than 12 months * positive for for glutamic acid decarboxylase antibody (gada), protein tyrosine phosphatase antibody (ia-2a), islet cell antibody (ica) and/or insulin autoantibody (iaas) exclusion criteria: * pregnancy * mental disorders * blood diseases * the presence of any other severe diseases that could potentially influence the transplantation outcomes

Keywords: type 1 diabetes stem cell c-peptide immune function